Thalassophilia and marine identity: Drivers of 'thick' marine citizenship.

Changing humanity's relationship with the ocean is identified as one of ten key challenges in the UN Decade of Ocean Science for Sustainable Development (2021-2030). Marine citizenship is one potential policy approach for reducing anthropogenic harms to the ocean and promoting ocean recovery, and there is a need to better understand marine citizenship motivating factors and their interactions. To contribute to a more holistic understanding, we approached this problem using an interdisciplinary, mixed methodology, which prioritised the voices and experiences of active marine citizens. An online survey and semi-structured interviews were conducted to examine factors spanning environmental psychology (values, environmental identity) and human geography (place attachment and dependency). Our data uncovered a unique marine place attachment, or thalassophilia, which is a novel conceptualisation of the human capacity to bond with a type of place beyond human settlements or defined localities. It is the product of strong emotional responses to the sensorial experience of the ocean and shared social or cultural understanding of ocean place identifications. A key driver of deeper marine citizenship is marine place dependency, and it is positively influence by stimulation and non-conformity values, environmental identity, and thalassophilia. We map significant motivating factors to identity process theory and describe a novel marine identity concept. We propose this as an operational mechanism of marine citizenship action, potentially filling the value- and knowledge-action gaps in the context of marine environmental action. This research provides a cornerstone in marine citizenship research by analysing together in one study a multitude of variables, which cross human-ocean relationships and experiences. The identification and characterisation of thalassophilia and marine identity process theory will enable research and practice to move forwards with a clearer framework of the role of the ocean as a place in environmental action.

Conceptualizing Trust and Distrust as Alternative Stable States: Lessons from the Flint Water Crisis.

Despite the universally recognized importance of fostering trust and avoiding distrust in governance relationships, there remains considerable debate on core questions like the relation between (dis)trust and the evaluations of the characteristics that make a governance agent appear (un)worthy of trust. In particular, it remains unclear whether levels of (dis)trust simply follow levels of (dis)trustworthiness-such that building trust is primarily a question of increasing evidence of trustworthiness and avoiding evidence of distrustworthiness, or if their dynamics are more complicated. The current paper adds novel theory for thinking about the management of trust and distrust in the governance context through the application of principles borrowed from resilience theory. Specifically, we argue that trust and distrust exist as distinct, self-reinforcing (i.e., stable) states separated by a threshold. We then theorize as to the nature of the self-reinforcing processes and use qualitative data collected from and inductively coded in collaboration with Flint residents as part of a participatory process to look for evidence of our argument in a well-documented governance failure. We conclude by explaining how this novel perspective allows for clearer insight into the experience of this and other communities and speculate as to how it may help to better position governance actors to respond to future crises.

A Quantitative Method to Measure the Kinetics of Elemental Mercury Emissions From Black Shale (Nova Scotia, Canada).

A controlled chamber method using continuous gold trap atomic fluorescence spectroscopy (AFS) (Tekran 2537X) for the analysis of Hg(0) emissions from moderate mass rock samples was developed and tested. A series of black shale and other bedrock samples from Nova Scotia, Canada, were used to test the method and its reproducibility. Hg(0) emissions at 170°C were measured to quantify both free surficial Hg(0) and Hg(0) that had penetrated the rock structure. High volumes of chamber air (45 L) were sampled using 30 min collection times to achieve detectable elemental mercury (Hg(0)) emissions. We found higher percentage masses of Hg(0) were released (1.1%-4.1% of total Hg mass present) in black shale samples as compared to granite and basalt samples from the same region (0.0%-0.3% released) over 350 h of continuous analysis time. The pseudo first order emission rate constants ranged from 0.015-0.245 h-1 (mean 0.063 h-1, standard deviation (SD) 0.102) for the black shale samples analyzed and was 0.004 h-1 for the granite sample. The 24-h zero-order emission rate constants ranged between 0.41 and 3.54 ng h-1 (mean 1.4 ng h-1, SD 1.3) for the black shale samples analyzed and were ~ 0.01 ng h-1 for the granite and basalt samples. This technique has useful implications for examining rock properties and Hg(0) emission rates.

An improved limit on the charge of antihydrogen from stochastic acceleration.

Antimatter continues to intrigue physicists because of its apparent absence in the observable Universe. Current theory requires that matter and antimatter appeared in equal quantities after the Big Bang, but the Standard Model of particle physics offers no quantitative explanation for the apparent disappearance of half the Universe. It has recently become possible to study trapped atoms of antihydrogen to search for possible, as yet unobserved, differences in the physical behaviour of matter and antimatter. Here we consider the charge neutrality of the antihydrogen atom. By applying stochastic acceleration to trapped antihydrogen atoms, we determine an experimental bound on the antihydrogen charge, Qe, of |Q| < 0.71 parts per billion (one standard deviation), in which e is the elementary charge. This bound is a factor of 20 less than that determined from the best previous measurement of the antihydrogen charge. The electrical charge of atoms and molecules of normal matter is known to be no greater than about 10(-21)e for a diverse range of species including H2, He and SF6. Charge-parity-time symmetry and quantum anomaly cancellation demand that the charge of antihydrogen be similarly small. Thus, our measurement constitutes an improved limit and a test of fundamental aspects of the Standard Model. If we assume charge superposition and use the best measured value of the antiproton charge, then we can place a new limit on the positron charge anomaly (the relative difference between the positron and elementary charge) of about one part per billion (one standard deviation), a 25-fold reduction compared to the current best measurement.

Computing committors via Mahalanobis diffusion maps with enhanced sampling data.

The study of phenomena such as protein folding and conformational changes in molecules is a central theme in chemical physics. Molecular dynamics (MD) simulation is the primary tool for the study of transition processes in biomolecules, but it is hampered by a huge timescale gap between the processes of interest and atomic vibrations that dictate the time step size. Therefore, it is imperative to combine MD simulations with other techniques in order to quantify the transition processes taking place on large timescales. In this work, the diffusion map with Mahalanobis kernel, a meshless approach for approximating the Backward Kolmogorov Operator (BKO) in collective variables, is upgraded to incorporate standard enhanced sampling techniques, such as metadynamics. The resulting algorithm, which we call the target measure Mahalanobis diffusion map (tm-mmap), is suitable for a moderate number of collective variables in which one can approximate the diffusion tensor and free energy. Imposing appropriate boundary conditions allows use of the approximated BKO to solve for the committor function and utilization of transition path theory to find the reactive current delineating the transition channels and the transition rate. The proposed algorithm, tm-mmap, is tested on the two-dimensional Moro-Cardin two-well system with position-dependent diffusion coefficient and on alanine dipeptide in two collective variables where the committor, the reactive current, and the transition rate are compared to those computed by the finite element method (FEM). Finally, tm-mmap is applied to alanine dipeptide in four collective variables where the use of finite elements is infeasible.

Evaluating the performance of temporal pattern discovery: new application using statins and rhabdomyolysis in OMOP databases.

BACKGROUND: Temporal pattern discovery (TPD) is a method of signal detection using electronic healthcare databases, serving as an alternative to spontaneous reporting of adverse drug events. Here, we aimed to replicate and optimise a TPD approach previously used to assess temporal signals of statins with rhabdomyolysis (in The Health Improvement Network (THIN) database) by using the OHDSI tools designed for OMOP data sources. METHODS: We used data from the Truven MarketScan US Commercial Claims and the Commercial Claims and Encounters (CCAE). Using an extension of the OHDSI ICTemporalPatternDiscovery package, we ran positive and negative controls through four analytical settings and calculated sensitivity, specificity, bias and AUC to assess performance. RESULTS: Similar to previous findings, we noted an increase in the Information Component (IC) for simvastatin and rhabdomyolysis following initial exposure and throughout the surveillance window. For example, the change in IC was 0.266 for the surveillance period of 1-30 days as compared to the control period of - 180 to - 1 days. Our modification of the existing OHDSI software allowed for faster queries and more efficient generation of chronographs. CONCLUSION: Our OMOP replication matched the we can account forwe can account for of the original THIN study, only simvastatin had a signal. The TPD method is a useful signal detection tool that provides a single statistic on temporal association and a graphical depiction of the temporal pattern of the drug outcome combination. It remains unclear if the method works well for rare adverse events, but it has been shown to be a useful risk identification tool for longitudinal observational databases. Future work should compare the performance of TPD with other pharmacoepidemiology methods and mining techniques of signal detection. In addition, it would be worth investigating the relative TPD performance characteristics using a variety of observational data sources.

Controlled synthesis of dicalcium phosphate dihydrate (DCPD) from metastable solutions: insights into pathogenic calcification.

Calcium phosphate (CaP) compounds may occur in the body as abnormal pathogenic phases in addition to their normal occurrence as bones and teeth. Dicalcium phosphate dihydrate (DCPD; CaPO4·2H2O), along with other significant CaP phases, have been observed in pathogenic calcifications such as dental calculi, kidney stones and urinary stones. While other studies have shown that polar amino acids can inhibit the growth of CaPs, these studies have mainly focused on hydroxyapatite (HAp; Ca10(PO4)6(OH)2) formation from highly supersaturated solutions, while their effects on DCPD nucleation and growth from metastable solutions have been less thoroughly explored. By further elucidating the mechanisms of DCPD formation and the influence of amino acids on those mechanisms, insights may be gained into ways that amino acids could be used in treatment and prevention of unwanted calcifications. The current study involved seeded growth of DCPD from metastable solutions at constant pH in the presence of neutral, acidic and phosphorylated amino acid side chains. As a comparison, solutions were also seeded with calcium pyrophosphate (CPP; Ca2P2O7), a known calcium phosphate inhibitor. The results show that polar amino acids inhibit DCPD growth; this likely occurs due to electrostatic interactions between amino acid side groups and charged DCPD surfaces. Phosphoserine had the greatest inhibitory ability of the amino acids tested, with an effect equal to that of CPP. Clustering of DCPD crystals giving rise to a "chrysanthemum-like" morphology was noted with glutamic acid. This study concludes that molecules containing an increased number of polar side groups will enhance the inhibition of DCPD seeded growth from metastable solutions.

Life expectancy inequalities in Wales before COVID-19: an exploration of current contributions by age and cause of death and changes between 2002 and 2018.

OBJECTIVES: The COVID-19 pandemic in Wales and the UK has highlighted significant and historic inequalities in health between social groups. To better understand the composition of these inequalities and inform planning after the pandemic, we undertook a decomposition of life expectancy inequalities between the most and least deprived quintiles for men and women by age and cause of death and explored trends between 2002 and 2018. STUDY DESIGN: Statistical decomposition of life expectancy inequalities by age and cause of death using routine population mortality datasets. METHODS: We used routine statistics from the Office for National Statistics for the period 2002-2018 on population and deaths in Wales stratified by age, gender, Welsh Index of Multiple Deprivation (WIMD) 2019 quintile and cause of death, categorised by International Classification of Disease, version 10, code into 15 categories of public health relevance. We aggregated data to 3-year rolling figures to account for low numbers of events in some groups annually. Next, we estimated life expectancy at birth by quintile, gender and period using life table methods. Lastly, we performed a decomposition analysis using the Arriaga method to identify the specific disease categories and ages at which excess deaths occur in more disadvantaged areas to highlight potential areas for action. RESULTS: Life expectancy inequalities between the most and least WIMD quintiles rose for both genders between 2002 and 2018: from 4.69 to 6.02 years for women (an increase of 1.33 years) and from 6.34 to 7.42 years for men (an increase of 1.08 years). Exploratory analysis of these trends suggested that the following were most influential for women: respiratory disease (1.50 years), cancers (1.36 years), circulatory disease (1.35 years) and digestive disease (0.51 years). For men, the gap was driven by circulatory disease (2.01 years), cancers (1.39 years), respiratory disease (1.25 years), digestive disease (0.79 years), drug- and alcohol-related conditions (0.54 years) and external causes (0.54 years). Contributions for women from respiratory disease, cancers, dementia and drug- and alcohol-related conditions appeared to be increasing, while among men, there were rising contributions from respiratory, digestive and circulatory disease. CONCLUSIONS: Life expectancy inequalities in Wales remain wide and have been increasing, particularly among women, with indications of worsening trends since 2010 following the introduction of fiscal austerity. As agencies recover from the pandemic, these findings should be considered alongside any resumption of services in Wales or future health and public policy.

Predicting population responses to environmental change from individual-level mechanisms: towards a standardized mechanistic approach.

Animal populations will mediate the response of global biodiversity to environmental changes. Population models are thus important tools for both understanding and predicting animal responses to uncertain future conditions. Most approaches, however, are correlative and ignore the individual-level mechanisms that give rise to population dynamics. Here, we assess several existing population modelling approaches and find limitations to both 'correlative' and 'mechanistic' models. We advocate the need for a standardized mechanistic approach for linking individual mechanisms (physiology, behaviour, and evolution) to population dynamics in spatially explicit landscapes. Such an approach is potentially more flexible and informative than current population models. Key to realizing this goal, however, is overcoming current data limitations, the development and testing of eco-evolutionary theory to represent interactions between individual mechanisms, and standardized multi-dimensional environmental change scenarios which incorporate multiple stressors. Such progress is essential in supporting environmental decisions in uncertain future conditions.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol.

Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in systemic therapy for advanced or metastatic prostate cancer: evaluation of drug efficacy: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC + AAP versus SOC + DocP. Method: Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2 years and RT to the primary tumour. Stratified randomisation allocated pts 2 : 1 : 2 to SOC; SOC + docetaxel 75 mg/m2 3-weekly×6 + prednisolone 10 mg daily; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily. AAP duration depended on stage and intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. This was not a formally powered comparison. A hazard ratio (HR) <1 favours SOC + AAP, and HR > 1 favours SOC + DocP. Results: A total of 566 consenting patients were contemporaneously randomised: 189 SOC + DocP and 377 SOC + AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66 years and median PSA 56 ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1.16 (95% CI 0.82-1.65); failure-free survival HR = 0.51 (95% CI 0.39-0.67); progression-free survival HR = 0.65 (95% CI 0.48-0.88); metastasis-free survival HR = 0.77 (95% CI 0.57-1.03); prostate cancer-specific survival HR = 1.02 (0.70-1.49); and symptomatic skeletal events HR = 0.83 (95% CI 0.55-1.25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC + DocP, and 40%, 7% and 1% SOC + AAP; prevalence 11% at 1 and 2 years on both arms. Relapse treatment patterns varied by arm. Conclusions: This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events. Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs. Trial registration: Clinicaltrials.gov: NCT00268476.

Interplay of hippocampal volume and hypothalamus-pituitary-adrenal axis function as markers of stress vulnerability in men at ultra-high risk for psychosis.

BACKGROUND: Altered hypothalamus-pituitary-adrenal (HPA) axis function and reduced hippocampal volume (HV) are established correlates of stress vulnerability. We have previously shown an attenuated cortisol awakening response (CAR) and associations with HV specifically in male first-episode psychosis patients. Findings in individuals at ultra-high risk (UHR) for psychosis regarding these neurobiological markers are inconsistent, and assessment of their interplay, accounting for sex differences, could explain incongruent results. METHOD: Study participants were 42 antipsychotic-naive UHR subjects (24 men) and 46 healthy community controls (23 men). Saliva samples for the assessment of CAR were collected at 0, 30 and 60 min after awakening. HV was determined from high-resolution structural magnetic resonance imaging scans using a semi-automatic segmentation protocol. RESULTS: Cortisol measures and HV were not significantly different between UHR subjects and controls in total, but repeated-measures multivariate regression analyses revealed reduced cortisol levels 60 min after awakening and smaller left HV in male UHR individuals. In UHR participants only, smaller left and right HV was significantly correlated with a smaller total CAR (ρ = 0.42, p = 0.036 and ρ = 0.44, p = 0.029, respectively), corresponding to 18% and 19% of shared variance (medium effect size). CONCLUSIONS: Our findings suggest that HV reduction in individuals at UHR for psychosis is specific to men and linked to reduced post-awakening cortisol concentrations. Abnormalities in the neuroendocrine circuitry modulating stress vulnerability specifically in male UHR subjects might explain increased psychosis risk and disadvantageous illness outcomes in men compared to women.

Differences in VigiBase® reporting of aminoglycoside and capreomycin-suspected ototoxicity during tuberculosis treatment.

PURPOSE: To evaluate the association between the use of streptomycin, amikacin, kanamycin and capreomycin in tuberculosis (TB) treatment and the pharmacovigilance reporting of ototoxicity (deafness or hearing loss, tinnitus and vertigo). Second, to analyze patient demographic and geographic factors that influence the reporting of ototoxicity in TB treatment. METHODS: A case/non-case disproportionality analysis of the VigiBase® individual case safety reports (ICSRs) of patients treated for TB using multidrug regimens that contain either of streptomycin, amikacin, kanamycin or capreomycin. Cases were reports of ototoxicity; non-cases were other adverse drug reactions (ADRs). The unit of analysis was the drug-ADR pair. We calculated reporting odds ratios (RORs) and their 95% confidence intervals (CI). The referent drug was streptomycin. RESULTS: By June 2014, there were 3361 drug-ADR pairs in VigiBase® (1693 ICSRs) where the parenteral administration of the four drugs for TB treatment was suspected of causing the reported ADRs. Deafness, tinnitus and vertigo were reported in 576 drug-ADR pairs (cases), the rest being other ADRs (non-cases). Reporting of deafness was most disproportionately associated with amikacin use (ROR 9.3; 95%CI 3.8-23.0), followed by kanamycin use (ROR 4.3; 95%CI 1.3-14.2). Reporting of vertigo was inversely associated with capreomycin use (ROR 0.1; 95%CI 0.01-0.4). Geographic region affected the reporting of ototoxicity while age and sex did not. CONCLUSION: Spontaneous reporting of deafness cases within VigiBase® was most disproportionately associated with amikacin use, followed by kanamycin. There were regional variations in the global reporting of ototoxicity. These findings should be verified through a follow up study. Copyright © 2016 John Wiley & Sons, Ltd.

Antimicrobial-resistant Faecal Organisms in Algae Products Marketed as Health Supplements.

Dietary supplements are increasingly popular in Irish society. One of these is blue-green algae which is used with a variety health benefits in mind. A batch of Chlorella powder was found to be contaminated with Salmonella species in Ireland in 2015. This prompted additional testing of a total of 8 samples of three different products (Chlorella, Spirulina and Super Greens), for other faecal flora and antimicrobial resistance in any bacteria isolated. All 8 samples cultured enteric flora such as Enterococci, Enterobacteriaceae and Clostridium species. Antimicrobial susceptibility testing revealed one isolate with extended-spectrum ?-lactamase (ESBL) activity and one with carbapenemase activity. Clinicians caring for vulnerable patients should be aware of the potential risk of exposure to antimicrobial resistant bacteria associated with these products.

CD8 T-cell responses against the immunodominant Theileria parva peptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes.

Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249-59 and Tp1214-224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide-MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298-106 ), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249-59 -reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250-59 represents a distinct epitope and that tetramers produced with Tp50-59 and Tp49-59 show no cross-reactivity. The Tp249-59 and Tp250-59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide-MHC I complexes adopt structurally different conformations and Tcell receptor ß sequence analysis showed that Tp249-59 and Tp250-59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249-59 and Tp250-59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214-224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249-59 epitope response was generally more dominant than the Tp250-59 response and confirmed that the Tp298-106 response was subdominant.

Electron Plasmas Cooled by Cyclotron-Cavity Resonance.

We observe that high-Q electromagnetic cavity resonances increase the cyclotron cooling rate of pure electron plasmas held in a Penning-Malmberg trap when the electron cyclotron frequency, controlled by tuning the magnetic field, matches the frequency of standing wave modes in the cavity. For certain modes and trapping configurations, this can increase the cooling rate by factors of 10 or more. In this Letter, we investigate the variation of the cooling rate and equilibrium plasma temperatures over a wide range of parameters, including the plasma density, plasma position, electron number, and magnetic field.

Geographical barriers and climate influence demographic history in narrowleaf cottonwoods.

Studies of genetic variation can clarify the role of geography and spatio-temporal variation of climate in shaping demography, particularly in temperate zone tree species with large latitudinal ranges. Here, we examined genetic variation in narrowleaf cottonwood, Populus angustifolia, a dominant riparian tree. Using multi-locus surveys of polymorphism in 363 individuals across the species' 1800 km latitudinal range, we found that, first, P. angustifolia has stronger neutral genetic structure than many forest trees (simple sequence repeat (SSR) FST=0.21), with major genetic groups corresponding to large apparent geographical barriers to gene flow. Second, using SSRs and putatively neutral sequenced loci, coalescent simulations indicated that populations diverged before the last glacial maximum (LGM), suggesting the presence of population structure before the LGM. Third, the LGM and subsequent warming appear to have had different influences on each of these distinct populations, with effective population size reduction in the southern extent of the range but major expansion in the north. These results are consistent with the hypothesis that climate and geographic barriers have jointly affected the demographic history of P. angustifolia, and point the importance of both factors as being instrumental in shaping genetic variation and structure in widespread forest trees.

Concurrent nonavalent human papillomavirus (HPV) vaccination and immune stimulation with imiquimod to treat recalcitrant HPV-associated high grade vaginal intra-epithelial neoplasia.

This is the first report describing detailed T cell responses to viral-like proteins contained in an HPV specific vaccine given in combination with Imiquimod for treatment of persistent VAIN2/3. We postulate that stimulation of the innate immune system with Imiquimod and the specific CD4 and CD8T cell responses following HPV vaccination with Gardasil9@ combined to induce clinical remission in a woman with treatment-refractory disease.

Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report.

BACKGROUND: Peri-operative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor. PATIENTS AND METHODS: ST03 is a multicentre, randomised, phase II/III study comparing peri-operative ECX with or without bevacizumab (ECX-B). The primary outcome measure of phase II (n = 200) was safety, specifically gastrointestinal (GI) perforation rates and cardiotoxicity. RESULTS: Two hundred patients were randomised between October 2007 and April 2010. Ninety-one/101 (90%) ECX and 86/99 (87%) ECX-B patients completed pre-operative chemotherapy; 7 ECX and 9 ECX-B patients stopped due to toxicity. Gastrointestinal perforations (3 ECX, 1 ECX-B), cardiac events (1 ECX, 4 ECX-B) and venous thromboembolic events (VTEs, 8 ECX, 7 ECX-B) were uncommon. Arterial thromboembolic events (ATEs, myocardial infarction (MI) or cerebrovascular accident) were more frequent with ECX-B (5 versus 1 with ECX). Delayed wound healing, anastomotic leaks and GI bleeding rates were similar. More asymptomatic left ventricular ejection fraction (LVEF) falls (≥15% and/or to <50%) occurred with ECX-B (21.2% versus 11.1% with ECX). Clinically significant falls (≥10% to below lower limit of normal, LLN) occurred in (15.3%) and (8.9%) respectively, with no associated cardiac failure (median 22 months follow-up). CONCLUSIONS: Addition of bevacizumab to peri-operative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes.

Inferring signalling networks from images.

The mapping of signalling networks is one of biology's most important goals. However, given their size, complexity and dynamic nature, obtaining comprehensive descriptions of these networks has proven extremely challenging. A fast and cost-effective means to infer connectivity between genes on a systems-level is by quantifying the similarity between high-dimensional cellular phenotypes following systematic gene depletion. This review describes the methodology used to map signalling networks using data generated in the context of RNAi screens.

Chlorhexidine droplet splash from a skin preparation gallipot: effect of height of pouring.

Chlorhexidine contamination of equipment used in central neuraxial anaesthesia has been implicated in causing adhesive arachnoiditis. We measured the extent of chlorhexidine splash during pouring into a gallipot (antiseptic skin preparation container) from heights of 5 cm, 10 cm, 15 cm and 20 cm. Twenty experiments were performed at each height. Measurements made up to a horizontal distance of 40 cm radius from the gallipot showed a median (IQR [range]) maximum spread of splash droplets ≥ 2 mm diameter of 26.2 (10.2-36.4 [0-40]) cm. The 40-cm radius measurement area was divided into 5-cm-wide zones to assess spread. At pouring heights of 15 cm and 20 cm, all zones were contaminated. These results demonstrate that pouring chlorhexidine into a gallipot generates significant splash, and we recommend that this should be avoided near equipment used for neuraxial anaesthesia.